Accurate Prediction of Secreted Substrates and Identification of a Conserved Putative Secretion Signal for Type III Secretion Systems

The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates—effector proteins—are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating protein sequence-based features, including evolutionary measures such as the pattern of homologs in a range of other organisms, G+C content, amino acid composition, and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from the plant pathogen Pseudomonas syringae and validated on a set of effectors from the animal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) after eliminating effectors with detectable sequence similarity. We show that this approach can predict known secreted effectors with high specificity and sensitivity. Furthermore, by considering a large set of effectors from multiple organisms, we computationally identify a common putative secretion signal in the N-terminal 20 residues of secreted effectors. This signal can be used to discriminate 46 out of 68 total known effectors from both organisms, suggesting that it is a real, shared signal applicable to many type III secreted effectors. We use the method to make novel predictions of secreted effectors in S. Typhimurium, some of which have been experimentally validated. We also apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis, identifying the majority of known secreted proteins in addition to providing a number of novel predictions. This approach provides a new way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal

Profiling Metabolites and Biological Activities of Sugarcane (Saccharum officinarum Linn.) Juice and Its Product Molasses via a Multiplex Metabolomics Approach

Sugarcane (Saccharum officinarum L.) is an important perennial grass in the Poaceae family cultivated worldwide due to its economical and medicinal value. In this study, a combined approach using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy was employed for the large-scale metabolite profiling of sugarcane juice and its by-product molasses. The polyphenols were analysed via UPLC-UV-ESI-MS, whereas the primary metabolites such as sugars and organic and amino acids were profiled using NMR spectroscopy and gas chromatography/mass spectrometry (GC/MS). UPLC/MS was more effective than NMR spectroscopy or GC/MS for determining differences among the metabolite compositions of the products. Under the optimized conditions, UPLC/MS led to the identification of 42 metabolites, including nine flavonoids, nine fatty acids, and two sterols. C/O Flavone glycosides were the main subclass detected, with tricin-7-O-deoxyhexosyl glucuronide being detected in sugarcane and molasses for the first time. Based on GC/MS analysis, disaccharides were the predominant species in the sugarcane juice and molasses, with sucrose accounting for 66% and 59%, respectively, by mass of all identified metabolites. The phenolic profiles of sugarcane and molasses were further investigated in relation to their in vitro antioxidant activities using free radical scavenging assays such as 2,2-Diphenyl-1-picrylhydrazyl free radical-scavenging ability (DPPH), Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). In view of its higher total phenolic content (TPC) (196 +/- 2.1 mg GAE/100 g extract) compared to that of sugarcane juice (93 +/- 2.9 mg GAE/100 g extract), molasses exhibited a substantially higher antioxidant effect. Interestingly, both extracts were also found to inhibit alpha-glucosidase and alpha-amylase enzymes, suggesting a possible antihyperglycaemic effect. These findings suggest molasses may be a new source of natural antioxidants for functional foods

Phytochemical And Biological Studies Of The Flowers And Fruits Of Pongamia Pinnata L.Pierre Growing In Egypt

The essential oil of the flowers of Pongamia pinnata L.Pierre was prepared by hydrodistillation and analysed using GS/MS technique. Thirty three components were identified, of which, β-citronellene (13.7%), limonene (13.35%) and trans caryophyllene (12.75%) were the major components. The retention indexes of the identified components were determined. GLC analysis of the fatty acid methyl esters prepared from the seed fixed oil and the petroleum ether extract of the flowers revealed the presence of oleic acid as the major fatty acid (84.8% and 34.86% respectively), while the major hydrocarbon detected in the unsaponifiable fraction was n-tetradecane (19.8%) and n-nonadecane (43.66%) respectively.Stigmasterol (3.12%) was the only sterol detected in the fixed oil of the seeds. The seed fixed oil and the aqueous and alcoholic extracts of the seed, flower and pericarp showed significant analgesic, antipyretic, anti-inflammatory, anti-ulcer and antidiabetic activities.Egyptian Journal of Biomedical Sciences Vol. 23 (1) 2007: pp. 1-1

Untersuchung von BSE-Nachkommen auf Protease-resistentes Prion Protein (PrPres) im Blut

Das Ziel der vorliegenden Arbeit war, zu untersuchen, ob im Blut von schweizerischen BSE-Nachkommen (Gruppe A) Protease-resistentes Prion Protein (PrPres) vorkommt und ob sich die Häufigkeit des Vorkommens von derjenigen einer gesunden Kontrollpopulation aus dem Jahr 2006 (Gruppe B) unterscheidet. Die Gruppe A bestand aus 181 Nachkommen von an BSE erkrankten Kühen, die Gruppe B aus 240 gesunden Rindern aus einem Gebiet, in welchem in den Jahren 2001 bis 2006 keine BSE diagnostiziert worden war. Die Blutproben wurden mit einem BSE-Lebendtest (Alicon PrioTrap®) zum Nachweis von Protease-resistentem Prion Protein untersucht. Um abzuklären, ob zwischen der Zeitdifferenz von der Geburt des Nachkommens bis zur Erkrankung der Mutter an BSE eine Beziehung in Bezug auf den Nachweis von PrPres beim Nachkommen bestand, wurde diese Zeitdauer bei jedem Nachkommen errechnet. Bei 29 (16.1 %) von 181 untersuchten BSE-Nachkommen wurde im Blutplasma PrPres nachgewiesen, 152 Tiere waren negativ. Nachkommen, die innerhalb eines Jahres vor dem Auftreten von klinischen Symptomen des Muttertieres geboren worden waren, wiesen im Blut signifikant häufiger PrPres auf als Tiere, bei denen der zeitliche Abstand von der Geburt bis zur Erkrankung mehr als ein Jahr betragen hatte (P < 0.05). In der Kontrollgruppe wurden 10 von 240 Tieren (4.2 %) positiv auf PrPres getestet. Die Untersuchungen haben gezeigt, dass beim Rind im Blut Protease-resistentes Prion Protein nachgewiesen werden kann und dass dieses bei Nachkommen von BSE-Kühen häufiger vorkommt als bei Tieren aus einer gesunden Kontrollpopulation

A common variant associated with prostate cancer in European and African populations

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldWith the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry